Pulmonary Multidrug-resistant Tuberculosis (MDR TB) MedDRA version: 14.1 Level: LLT Classification code 10037443 Term: Pulmonary tuberculosis, unspecified System Organ Class: 100000004862
Conditions
Interventions
Product Name: Delamanid
Product Code: OPC-67683
Pharmaceutical Form: Tablet
INN or Proposed INN: Delamanid
CAS Number: 681492-22-8
Current Sponsor code: OPC-67683
Other descriptive name: Delamanid
Con
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Provide written, informed consent prior to all trial-related procedures. Male or female patients aged between 18 and 69 years, inclusive. Current Diagnosis of MDR TB from one of the following methods: • From a single sputum specimen collected no more than 60 days prior to the date of trial enrollment (defined as the date the ICF is signed and screening begins), mycobacterial culture positive for growth of MTB with documented resistance to isoniazid and rifampicin, OR • From a single sputum specimen collected no more than 60 days prior to date of trial enrollment (defined as the date the ICF is signed and screening begins), sputum smear positive for acid fast bacilli (AFB) with positive rapid tests for isoniazid and rifampicin resistance. Findings on screening chest radiograph consistent with TB. Able to produce sputum for mycobacterial culture. Female patients of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, IUD, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation). Male patients must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose (to cover duration of spermatogenesis). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time. Use of the medications in Section 4.1 including: use of amiodarone at any time during the previous 12 months or use of other anti-arrhthymics for the previous 30 days. Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels greater or equal 1.5 mg/dL or hepatic impairment characterized by ALT and/or AST levels 3 times the upper limit of the laboratory reference range. Current clinically relevant abnormalities in the screening ECG including conduction abnormalities (AV block or hemiblock) or QTcF interval over 450 msec in male patients and 470 msec in female patients. Current clinically relevant/significant cardiovascular disorder such as congestive heart failure, ventricular hypertrophy, coronary artery disease, arrhythmia, or poorly controlled hypertension. BMI < 16 kg/m2. Karnofsky score < 50%. Any diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated. Evidence of currently active clinically significant metabolic, gastrointestinal, neurological, psychiatric, or endocrine diseases (eg, poorly controlled diabetes mellitus), currently active malignancy, or other abnormalities (other than those related to the indication being studied). Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the patient in the opinion of the investigator. Administered an IMP within 1 month prior to Visit 1 (Screening [Days -21 to -2]). Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the ICF. Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, and opiates as determined by a urine drug screen unless evidence is provided that the positive drug screen is the result of authorized medications prescribed by a physician for a nonabuse-related indication. Any disorder that in the judgment of the investigator makes the patient not a good candidate for the trial or may prevent the patient from reliably participating in the entire course of the trial. Previous exposure to delamanid. Evidence of XDR TB based on the definition from WHO as TB with demonstrated resistance to isoniazid and rifampicin as well to any one of the fluoroquinolones and at least one of three injectable second-line drugs (amikacin, capreomycin, or kanamycin). HIV co-infection for patients screened at sites not participating in the HIV subtrial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to evaluate the efficacy of delamanid administered orally as 100 mg twice daily (BID) for 2 months followed by 200 mg once daily (QD) for 4 months in combination with an optimized background regimen (OBR) versus placebo with OBR during the 6-month intensive phase of MDR TB treatment. Efficacy will be assessed by comparing the proportion of patients achieving sputum culture conversion (SCC) from growth of Mycobacterium tuberculosis (MTB) to no growth of MTB after 2 months of treatment as well as distribution of time to SCC between the two treatment groups during the 6-month Intensive Treatment Period of MDR TB treatment.;Secondary Objective: • To evaluate the safety of delamanid administered orally as 100 mg BID for 2 months followed by 200 mg QD for 4 months in combination with OBR versus placebo with OBR during the 6-month Intensive Treatment Period • To evaluate pharmacokinetics (PK) of delamanid administered orally as 100 mg BID for 2 months followed by 200 mg QD for 4 months during the 6-month Intensive Treatment Period as part of a population PK analysis. • To evaluate the durability of SCC achieved by patients from the two treatment groups during the 6-month Intensive Treatment Period, through the 12 to 18-month Continuation Treatment Period, and until the end of the Post-Treatment Follow-up Period at Month 30. • To evaluate final treatment outcomes as defined by WHO for patients at the end of the 18 to 24-month full treatment period for MDR TB;Primary end point(s): The primary efficacy endpoints are (1) proportion of patients achieving SCC at 2 months (8 weeks) using MGIT, and (2) distribution of the time to SCC using the MGIT system during the 6-month Intensive Treatment Period. SCC is defined as a sputum specimen from a patient negative for growth of MTB using the MGIT culture system, followed by at least one confirmatory negative sputum culture at least 27 days after the first negative sputum and no | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Intensive Treatment Period (Weeks 1 through 26): • Proportion of patients with SCC at 2 months using solid culture media • Distribution of time to SCC (using the same definition as for the primary endpoint) using solid culture media • Proportion of patients with SCC at 6 months using MGIT. • Proportion of patients with SCC at 6 months using solid culture media Continuation Treatment Period (Months 7 through 18 to 24) and Post-treatment follow up period (Months 19 to 24 through Month 30): • Durability of SCC with the MGIT system during the Continuation Treatment and Post-treatment Follow-up periods at Month 18. • Durability of SCC with the MGIT system during the Continuation Treatment and Post-treatment Follow-up periods at Month 30. ;Timepoint(s) of evaluation of this end point: see section E.5.2 | — |
Countries
Estonia, India, Latvia, Lithuania, Moldova, Republic of, Peru, Philippines, South Africa
Contacts
Public ContactMedical Director
Otsuka Pharmaceutical Development & Commercialization, Inc.
Outcome results
None listed